Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1983 Feb;3(2):214–219. doi: 10.1128/mcb.3.2.214

Mutational analysis of simian virus 40 T antigen: stimulation of cellular DNA synthesis and activation of rRNA genes by mutants with deletions in the T-antigen gene.

K J Soprano, N Galanti, G J Jonak, S McKercher, J M Pipas, K W Peden, R Baserga
PMCID: PMC368524  PMID: 6300657

Abstract

The biological activity of several deletion mutants of simian virus 40, cloned in pBR322, was determined. Three functions of the simian virus 40 A gene were studied: (i) the ability to express T antigen; (ii) the ability to induce cell DNA replication; and (iii) the ability to reactivate silent rRNA genes in hybrid cells. Recombinant plasmid DNA was introduced into cells by manual microinjection or by transfection. The results (together with previous reports) indicate that the critical sequences for these three functions are located separately on the simian virus 40 A gene, as follows: (i) the sequences necessary for the detection of the common antigenic determinant of T antigen extend from nucleotide 4147 to nucleotide 4001 (map units 0.45 to 0.42); (ii) the sequences critical for the stimulation of cell DNA synthesis extend from nucleotide 4327 to nucleotide 4001 (map units 0.49 to 0.42); and (iii) those critical for the reactivation of rRNA genes extend approximately from nucleotide 3827 to nucleotide 3526 (map units 0.39 to 0.33).

Full text

PDF
214

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alwine J. C., Reed S. I., Stark G. R. Characterization of the autoregulation of simian virus 40 gene A. J Virol. 1977 Oct;24(1):22–27. doi: 10.1128/jvi.24.1.22-27.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brockman W. W. Transformation of BALB/c-3T3 cells by tsA mutants of simian virus 40: temperature sensitivity of the transformed phenotype and retransofrmation by wild-type virus. J Virol. 1978 Mar;25(3):860–870. doi: 10.1128/jvi.25.3.860-870.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brugge J. S., Butel J. S. Role of simian virus 40 gene A function in maintenance of transformation. J Virol. 1975 Mar;15(3):619–635. doi: 10.1128/jvi.15.3.619-635.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chou J. Y., Martin R. G. DNA infectivity and the induction of host DNA synthesis with temperature-sensitive mutants of simian virus 40. J Virol. 1975 Jan;15(1):145–150. doi: 10.1128/jvi.15.1.145-150.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cowan K., Tegtmeyer P., Anthony D. D. Relationship of replication and transcription of Simian Virus 40 DNA. Proc Natl Acad Sci U S A. 1973 Jul;70(7):1927–1930. doi: 10.1073/pnas.70.7.1927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Croce C. M. Loss of mouse chromosomes in somatic cell hybrids between HT-1080 human fibrosarcoma cells and mouse peritioneal macrophages. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3248–3252. doi: 10.1073/pnas.73.9.3248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Croce C. M., Talavera A., Basilico C., Miller O. J. Suppression of production of mouse 28S ribosomal RNA in mouse-human hybrids segregating mouse chromosomes. Proc Natl Acad Sci U S A. 1977 Feb;74(2):694–697. doi: 10.1073/pnas.74.2.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Floros J., Jonak G., Galanti N., Baserga R. Induction of cell DNA replication in G1-specific ts mutants by microinjection of SV40 DNA. Exp Cell Res. 1981 Mar;132(1):215–223. doi: 10.1016/0014-4827(81)90097-5. [DOI] [PubMed] [Google Scholar]
  9. Galanti N., Jonak G. J., Soprano K. J., Floros J., Kaczmarek L., Weissman S., Reddy V. B., Tilghman S. M., Baserga R. Characterization and biological activity of cloned simian virus 40 DNA fragments. J Biol Chem. 1981 Jun 25;256(12):6469–6474. [PubMed] [Google Scholar]
  10. Graessmann M., Graessman A. "Early" simian-virus-40-specific RNA contains information for tumor antigen formation and chromatin replication. Proc Natl Acad Sci U S A. 1976 Feb;73(2):366–370. doi: 10.1073/pnas.73.2.366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hiscott J. B., Defendi V. Simian virus 40 gene A regulation of cellular DNA synthesis. I. In permissive cells. J Virol. 1979 May;30(2):590–599. doi: 10.1128/jvi.30.2.590-599.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hiscott J. B., Defendi V. Simian virus 40 gene A regulation of cellular DNA synthesis. II. In nonpermissive cells. J Virol. 1981 Feb;37(2):802–812. doi: 10.1128/jvi.37.2.802-812.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Khoury G., May E. Regulation of early and late simian virus 40 transcription: overproduction of early viral RNA in the absence of a functional T-antigen. J Virol. 1977 Jul;23(1):167–176. doi: 10.1128/jvi.23.1.167-176.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kimura G., Dulbecco R. A temperature-sensitive mutant of simian virus 40 affecting transforming ability. Virology. 1973 Apr;52(2):529–534. doi: 10.1016/0042-6822(73)90348-6. [DOI] [PubMed] [Google Scholar]
  15. Kimura G., Itagaki A. Initiation and maintenance of cell transformation by simian virus 40: a viral genetic property. Proc Natl Acad Sci U S A. 1975 Feb;72(2):673–677. doi: 10.1073/pnas.72.2.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kirschner K., Bisswanger H. Multifunctional proteins. Annu Rev Biochem. 1976;45:143–166. doi: 10.1146/annurev.bi.45.070176.001043. [DOI] [PubMed] [Google Scholar]
  17. Martin R. G., Chou J. Y. Simian virus 40 functions required for the establishment and maintenance of malignant transformation. J Virol. 1975 Mar;15(3):599–612. doi: 10.1128/jvi.15.3.599-612.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. May P., May E., Bordé J. Stimulation of cellular RNA synthesis in mouse-kidney cell cultures infected with SV40 virus. Exp Cell Res. 1976 Jul;100(2):433–436. doi: 10.1016/0014-4827(76)90175-0. [DOI] [PubMed] [Google Scholar]
  19. Mueller C., Graessmann A., Graessmann M. Mapping of early SV40-specific functions by microinjection of different early viral DNA fragments. Cell. 1978 Oct;15(2):579–585. doi: 10.1016/0092-8674(78)90026-0. [DOI] [PubMed] [Google Scholar]
  20. Oda K., Dulbecco R. Induction of cellular mRNA synthesis in BSC-1 cells infected by SV40. Virology. 1968 Jul;35(3):439–444. doi: 10.1016/0042-6822(68)90222-5. [DOI] [PubMed] [Google Scholar]
  21. Osborn M., Weber K. Simian virus 40 gene A function and maintenance of transformation. J Virol. 1975 Mar;15(3):636–644. doi: 10.1128/jvi.15.3.636-644.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. POPE J. H., ROWE W. P. DETECTION OF SPECIFIC ANTIGEN IN SV40-TRANSFORMED CELLS BY IMMUNOFLUORESCENCE. J Exp Med. 1964 Aug 1;120:121–128. doi: 10.1084/jem.120.2.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Peden K. W., Pipas J. M., Pearson-White S., Nathans D. Isolation of mutants of an animal virus in bacteria. Science. 1980 Sep 19;209(4463):1392–1396. doi: 10.1126/science.6251547. [DOI] [PubMed] [Google Scholar]
  24. Pipas J. M., Adler S. P., Peden K. W., Nathans D. Deletion mutants of SV40 that affect the structure of viral tumor antigens. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):285–291. doi: 10.1101/sqb.1980.044.01.032. [DOI] [PubMed] [Google Scholar]
  25. Pipas J. M., Peden K. W., Nathans D. Mutational analysis of simian virus 40 T antigen: isolation and characterization of mutants with deletions in the T-antigen gene. Mol Cell Biol. 1983 Feb;3(2):203–213. doi: 10.1128/mcb.3.2.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pöckl E., Wintersberger E. Increased rate of RNA synthesis: early reaction of primary mouse kidney cells to infection with polyoma virus of simian virus 40. J Virol. 1980 Jul;35(1):8–19. doi: 10.1128/jvi.35.1.8-19.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reed S. I., Stark G. R., Alwine J. C. Autoregulation of simian virus 40 gene A by T antigen. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3083–3087. doi: 10.1073/pnas.73.9.3083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sauer G., Defendi V. Stimulation of DNA synthesis and complement-fixing antigen production by SV40 in human diploid cell cultures: evidence for "abortive" infection. Proc Natl Acad Sci U S A. 1966 Aug;56(2):452–457. doi: 10.1073/pnas.56.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Scott W. A., Brockman W. W., Nathans D. Biological activities of deletion mutants of simian virus 40. Virology. 1976 Dec;75(2):319–334. doi: 10.1016/0042-6822(76)90031-3. [DOI] [PubMed] [Google Scholar]
  30. Soprano K. J., Dev V. G., Croce C. M., Baserga R. Reactivation of silent rRNA genes by simian virus 40 in human-mouse hybrid cells. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3885–3889. doi: 10.1073/pnas.76.8.3885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Soprano K. J., Jonak G. J., Galanti N., Floros J., Baserga R. Identification of an SV40 DNA sequence related to the reactivation of silent rRNA genes in human greater than mouse hybrid cells. Virology. 1981 Feb;109(1):127–136. doi: 10.1016/0042-6822(81)90477-3. [DOI] [PubMed] [Google Scholar]
  32. Soprano K. J., Rossini M., Croce C., Baserga R. The role of large T antigen in simian virus 40-induced reactivation of silent rRNA genes in human-mouse hybrid cells. Virology. 1980 Apr 30;102(2):317–326. doi: 10.1016/0042-6822(80)90099-9. [DOI] [PubMed] [Google Scholar]
  33. Stringer J. R. Mutant of simian virus 40 large T-antigen that is defective for viral DNA synthesis, but competent for transformation of cultured rat cells. J Virol. 1982 Jun;42(3):854–864. doi: 10.1128/jvi.42.3.854-864.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tegtmeyer P. Function of simian virus 40 gene A in transforming infection. J Virol. 1975 Mar;15(3):613–618. doi: 10.1128/jvi.15.3.613-618.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tegtmeyer P., Schwartz M., Collins J. K., Rundell K. Regulation of tumor antigen synthesis by simain virus 40 gene A. J Virol. 1975 Jul;16(1):168–178. doi: 10.1128/jvi.16.1.168-178.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tegtmeyer P. Simian virus 40 deoxyribonucleic acid synthesis: the viral replicon. J Virol. 1972 Oct;10(4):591–598. doi: 10.1128/jvi.10.4.591-598.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Tjian R., Fey G., Graessmann A. Biological activity of purified simian virus 40 T antigen proteins. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1279–1283. doi: 10.1073/pnas.75.3.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Weil R., Salomon E., May E., May P. A simplifying concept in tumor virology: virus-specific "pleiotropic effectors". Cold Spring Harb Symp Quant Biol. 1975;39(Pt 1):381–395. doi: 10.1101/sqb.1974.039.01.050. [DOI] [PubMed] [Google Scholar]
  39. Weil R. Viral 'tumor antigens': A novel type of mammalian regulator protein. Biochim Biophys Acta. 1978 Nov 17;516(3):301–388. doi: 10.1016/0304-419x(78)90012-4. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES